Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
Eur J Cardiothorac Surg. 2010 Jun;37(6):1411-20. doi: 10.1016/j.ejcts.2010.01.001. Epub 2010 Feb 10.
Pulmonary dysfunction following lung ischaemia-reperfusion is a well-known phenomenon, which may contribute to post-cardiac surgical morbidity. The process is associated with pulmonary inflammatory response and cellular apoptosis. Early molecular mechanisms leading to such lung injury remain largely unknown. We examined whether lung ischaemia and reperfusion cause significant expression changes in numerous genes in the lungs involved in pulmonary apoptosis and other cellular processes by using oligonucleotide microarrays in an experimental model of rodent lung ischaemia-reperfusion injury.
Sprague-Dawley rodents (n=5 in each group) were anaesthetised and underwent controlled ventilation, with varying durations of warm lung ischaemia (60 and 90 min) followed by a short reperfusion period. The right middle lobe of the lung was harvested. Gene expression changes in the lungs were analysed by rodent DNA microarray chips, and reverse transcription polymerase chain reaction (RT-PCR) performed to validate changes in gene expression.
Significant expression changes, with reference to false discovery rate (FDR) controls, were detected in over 80 genes following controlled lung ventilation, and more than 50 were up-regulated more than 2-fold. Lung ischaemia-reperfusion caused expression changes in over 50 additional genes, including many novel genes not previously associated with lung ischaemia-reperfusion. Up-regulated genes identified include those associated with apoptosis, inflammation and cell-cycle control.
Large numbers of genes relating to cell metabolism, transcription control, inflammation and apoptosis were significantly up- and down-regulated following controlled ventilation and early lung ischaemia-reperfusion, consistent with previous studies. In addition, novel genes related to lung injury were identified. These genetic signatures provide new insights into early molecular mechanisms of ischaemia-reperfusion lung injury and help refine therapeutic strategies to lessen pulmonary dysfunction following cardiac surgery.
肺缺血再灌注后出现的肺功能障碍是一种众所周知的现象，可能导致心脏手术后发病率升高。这一过程与肺部炎症反应和细胞凋亡有关。导致这种肺损伤的早期分子机制在很大程度上仍不清楚。我们通过在啮齿动物肺缺血再灌注损伤的实验模型中使用寡核苷酸微阵列，研究了肺缺血和再灌注是否会导致参与肺细胞凋亡和其他细胞过程的大量肺部基因发生显著表达变化。
将 Sprague-Dawley 啮齿动物（每组 5 只）麻醉并进行控制性通气，分别经历不同时间的温肺缺血（60 分钟和 90 分钟），然后进行短暂的再灌注期。收获右中叶肺。通过啮齿动物 DNA 微阵列芯片分析肺内基因表达变化，并进行逆转录聚合酶链反应（RT-PCR）验证基因表达变化。
在控制性通气后，超过 80 个基因的表达发生了显著变化，超过 50 个基因的表达上调了 2 倍以上。肺缺血再灌注导致 50 多个额外基因的表达发生变化，其中包括许多以前与肺缺血再灌注无关的新基因。上调的基因包括与细胞凋亡、炎症和细胞周期控制相关的基因。
在控制性通气和早期肺缺血再灌注后，大量与细胞代谢、转录控制、炎症和凋亡相关的基因显著上调和下调，与之前的研究一致。此外，还鉴定出了与肺损伤相关的新基因。这些遗传特征为缺血再灌注肺损伤的早期分子机制提供了新的见解，并有助于完善治疗策略，减轻心脏手术后的肺部功能障碍。
